Three forms of the glycolytic enzyme, enolase have been identified in brain, a neuronal-specific enolase (NSE), a non-neuronal enolase (NNE) and a hybrid species localized in neurons and composed of subunits of NSE and NNE. Recently, a new enzyme assay was developed that readily separates and independently measures the activity of each form of enolase. As demonstrated in this laboratory and others, this new method can be used to quantitate the neuronal degeneration in lesioned rat brains. The advantage of NSE as a specific neuronal enzyme marker over that of other neuronal specific proteins is that NSE is present ubiquitously in neuronal cells regardless of their neurotransmitter class. Recent studies have reported finding an increase in the levels of NSE in the CSF of patients with severe anoxic coma and loss of NSE in brains of patients with Huntingtons disease. Whether alterations in NSE in brain or the CSF can also be observed under less severe neurological conditions, however, is not known. Accordingly, the majora aim of the project is: Examine the levels of the three forms of enolase in rat CSF under experimental conditions which are known to produce different degrees of nerve cell degeneration or alter the levels of NSE in brain. The experimental conditions include: a) kainic acid lesions of striata; b) ischemic lesions with and without blood-brain barrier breakdown; c) treatment with several pharmacological agents previously reported to increase brain NSE. Data obtained from these experiments will provide useful information for determining 1) whether the new method for measuring the three forms of enolase is applicable for assessing neuronal degeneration, 2) whether the degeneration of nerve cells caused by kainic acid and ischemic lesioning are reflected by increased concentrations of NSE in rat CSF, 3) whether NSE can be regulated by drugs or hormones and 4) whether changes in the cellular content of NSE effect the levels of NSE present in the CSF. This investigation may prove applicable in future studies in which NSE is measured in the CSF of humans to detect neurological and/or behavioral disorders.